Dimethylformamide → Methyl 5-(thiazol-4-ylmethoxy)pyrazine-2-carboxylate

HRID 1526597

Reaction equation

HRID 1526597 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[S:12]1[CH:16]=[C:15]([CH2:17][OH:18])[N:14]=[CH:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>O>[S:12]1[CH:16]=[C:15]([CH2:17][O:18][C:2]2[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=2)[N:14]=[CH:13]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 2763215(1,3-Thiazol-4-yl)methanol

Product 1

HCID 90389321Methyl 5-(thiazol-4-ylmethoxy)pyrazine-2-carboxylateYield 42.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

A RBF was charged with methyl 5-chloropyrazine-2-carboxylate (1.239 g, 7.18 mmol, Ark Pharm), thiazol-4-ylmethanol (0.8266 g, 7.18 mmol), cesium carbonate (0.689 ml, 8.61 mmol, Alfa Aesar) and DMF (20.51 ml). The reaction mixture was stirred at 40° C. for 3 days. The reaction mixture was allowed to cool to rt and was diluted with water and extracted with EtOAc. The organic extract was washed with water, satd NaCl, dried over MgSO4, and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and purified by silica gel flash chromatography, eluting with a gradient of 10% to 100% EtOAc in hexane, to provide methyl 5-(thiazol-4-ylmethoxy)pyrazine-2-carboxylate (0.7606 g, 3.03 mmol, 42.2% yield). MS m/z=252.1 [M+H]+. Calculated for C10H9N3O3S: 251.036. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.89 (s, 2H) 5.60 (s, 1H) 7.86 (d, J=1.96 Hz, 1H) 8.46 (d, J=1.37 Hz, 1H) 8.86 (d, J=1.37 Hz, 1H) 9.14 (d, J=1.96 Hz, 1H)

Workup

  1. temperatureto cool to rt
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel flash chromatography
  8. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-c0801f5801694ff6a152d83ac632dbb4
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Linked notes

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